Tetrahydrofuran Solvate Research Articles

Exploring the thermal behaviour of the solvated structures of nifedipine.

Understanding the solvation and desolvation of pharmaceutical materials is an important part of materials discovery and development. In situ structural data are vital to understand the changes to crystal form that may occur in the system. In this study, the isolation and characterization of seven solvates of the L-type calcium channel antagonist, nifedipine, is described using variable-temperature powder X-ray diffraction so that the structural evolution as a function of temperature can be followed. The solvates reported herein can be split into those that are structurally similar to the previously reported dimethyl sulfoxide (DMSO) and dioxane solvates and those that have a novel packing arrangement. Of particular note is the solvate with tetrahydrofuran (THF) which has a hydrogen-bonding motif between the nifedipine molecules very similar to that of metastable β-nifedipine. In addition to variable-temperature X-ray diffraction, the stability of the solid forms was assessed using differential scanning calorimetry and thermogravimetric analysis and indicates that in all cases desolvation results in the thermodynamically stable α-polymorph of nifedipine even with the THF solvate. From the diffraction data the pathway of desolvation during heating of the DMF solvate showed conversion to another likely 1:1 polymorph before desolvation to α-nifedipine. The desolvation of this material indicated a two-stage process; first the initial loss of 90% of the solvent before the last 10% is lost on melting. The methanol solvate shows interesting negative thermal expansion on heating, which is rarely reported in organic materials, but this behaviour can be linked back to the winerack-type hydrogen-bonding pattern of the nifedipine molecules.

Introducing Benzene-1,3,5-tri(dithiocarboxylate) as a Multidentate Linker in Coordination Chemistry.

Benzene-1,3,5-tri(dithiocarboxylate) (BTDTC3-), the sulfur-donor analogue of trimesate (BTC3-, benzene-1,3,5-tricarboxylate), is introduced, and its potential as a multidentate, electronically bridging ligand in coordination chemistry is evaluated. For this, the sodium salt Na3BTDTC has been synthesized, characterized, and compared with the sodium salt of the related ditopic benzene-1,4-di(dithiocarboxylate) (Na2BDDTC). Single-crystal X-ray diffraction of the respective tetrahydrofuran (THF) solvates reveals that such multitopic aromatic dithiocarboxylate linkers can form both discrete metal complexes (Na3BTDTC·9THF) and (two-dimensional) coordination polymers (Na2BDDTC·4THF). Additionally, the versatile coordination behavior of the novel BTDTC3- ligand is demonstrated by successful synthesis and characterization of trinuclear Cu(I) and hexanuclear Mo(II)2 paddlewheel complexes. The electronic structure and molecular orbitals of both dithiocarboxylate ligands as well as their carboxylate counterparts are investigated by density functional theory computational methods. Electrochemical investigations suggest that BTDTC3- enables electronic communication between the coordinated metal ions, rendering it a promising tritopic linker for functional coordination polymers.

Maleate salts of bedaquiline.

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-meth-oxy-quinolin-3-yl)-3-hy-droxy-3-(naphthalen-1-yl)-4-phenyl-but-yl]di-methyl-aza-nium 3-carb-oxy-prop-2-enoate}, C32H32BrN2O2 +·C4H3O4 -, namely, a hemihydrate, a tetra-hydro-furan (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by in situ single-crystal-to-single-crystal desolvation. All salts exhibit a 1:1 cation-to-anion ratio, with the anion present as monoanionic hydro-maleate and a singly protonated bedaquilinium cation. The maleate exhibits the strong intra-molecular hydrogen bond typical for cis-di-carb-oxy-lic acid anions. The conformations of the cations and packing inter-actions in the maleate salts are compared to those of free base bedaquiline and other bedaquilinium salts.

STRUCTURE OF A Pd–ORGANIC PARAMAGNETIC

By the interaction of 2-bromo-4,4,5,5-tetramethyl-2-imidazoline-3-oxide-1-oxyl (NN–Br) with tetrakis(triphenylphosphine)palladium(0) a new paramagnetic palladium-organic compound [Pd(NN)(PPh3)2Br] is synthesized. The crystal structure of its tetrahydrofuran solvate is determined by X-ray diffraction. The obtained data allow us to expect that the effective Pd–C bond eclipsing by phenyl rings deactivates the compound in a cross-coupling reaction with aryl halides and provides its high kinetic stability under normal conditions. Magnetochemical studies show the presence of weak antiferromagnetic exchange interactions between spins of paramagnetic [Pd(NN)(PPh3)2Br].

10-Phenyl-10H-phenoxazine-4,6-diol tetra-hydro-furan monosolvate.

In the crystalline state of the title solvate, C18H13NO3·C4H8O, hydrogen-bonding inter-actions between hydroxyl groups on a phenoxazine backbone and the tetra-hydro-furan solvent are observed that suggest the ability for this compound to act as a chelating ligand. The O⋯O donor-acceptor distances for this hydrogen bonding are 2.7729 (15) and 2.7447 (15) Å. The three-ring backbone of the phenoxazine bends out of planarity by 18.92 (3)°, as computed using mean planes that encompass each half of the three-ring structure, with the central N and O atoms forming the line of flexion. In the crystal, a π-π stacking arrangement exists between inversion-related mol-ecules, with a centroid-to-centroid distance of 3.6355 (11) Å. In the disordered tetra-hydro-furan solvate, all atoms except oxygen were modeled over two positions, with occupancies of 0.511 (8) and 0.489 (8).

COMF: Comprehensive Model-Fitting Method for Simulating Isothermal and Single-Step Solid-State Reactions

It is well known that the implementation of the conventional model-fitting (CMF) method leads to several indistinguishable ‘best’ candidate models (BCMs) for a single-step isothermal solid-state reaction (ISSR), meaning that subjective selection becomes unavoidable. Here, we developed a more robust comprehensive model-fitting method (COMF) which, while maintaining the mathematical simplicity of CMF, utilizes a ranking criterion that enables automatic and unambiguous determination of the BCM. For each model evaluated, COMF, like CMF, fits the integral reaction rate, but, unlike CMF, it also fits the experimental conversion fraction and reaction speed. From this, three different determination coefficients are calculated and combined to rank the considered models. To validate COMF, we used two sets of experimental kinetic data from the literature regarding the isothermal desolvation of pharmaceutical solvates: (i) tetrahydrofuran solvates of sulfameter, and (ii) methanol solvates of ciclesonide. Our results suggest that from an algorithmic perspective, COMF could become the model-fitting method of choice for ISSRs making the selection of BCM easier and more reliable.

Isostructural Solvates of Naturally Occurring Allocryptopine Exhibit Both Mechanochromic and Hydrochromic Luminescent Properties.

We discovered four new solvates for naturally sourced allocryptopine. The new found crystalline forms are isostructural and have similar crystal structures and packing patterns. However, they exhibit obviously different fluorescence appearance. In addition, the acetone solvate SA, N,N-dimethylformamide solvate SD, and tetrahydrofuran solvate ST also present both luminescent mechanochromic and hydrochromic properties.

Synthesis of Two Lead Complexes of Propellant Stabilizer Compounds: In Pursuit of Novel Propellant Additives

AbstractTwo lead complexes, Tetrakis(μ3‐(4‐methyl‐3‐nitrophenyl imido lead (II))) 1, and Bis(2‐nitrodiphenyl amido lead(II)) 2, were prepared by protolysis of bis(bis(trimethylsilyl)amido)lead(II) with two compounds relevant to double‐base propellant stabilizers: 2‐nitrodiphenylamine (NDPA) and 4‐methyl‐3‐nitroaniline. Crystal structures were determined as tetrahydrofuran solvates, and exhibit a number of unusual geometric features, including low lead coordination number. Heats of combustion and formation were determined using bomb calorimetry and converted to energy density using crystallographic densities. Compound 1 has an energy density of 30 MJ/L, whereas 2 was 38.2 MJ/L.

Epalrestat tetra-hydro-furan monosolvate: crystal structure and phase transition.

The title compound, epalrestat {systematic name: (5Z)-5-[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl-idene]-4-oxo-2-sulfanyl-idene-1,3-thia-zolidine-3-acetic acid}, crystallized as a tetra-hydro-furan monosolvate, C15H13NO3S2·C4H8O. Epalrestat, an important drug for diabetic neuropathy, has been reported to exist in polymphic, solvated and co-crystal forms. In the mol-ecule reported here, the phenyl ring is inclined to the rhodamine ring by 22.31 (9)°, and the acetic acid group is almost normal to the rhodamine ring, making a dihedral angle of 88.66 (11)°. In the crystal, pairs of O-H⋯O hydrogen bonds are observed between the carb-oxy-lic acid groups of epalerstat mol-ecules, forming inversion dimers with an R22(8) loop. The dimers are linked by pairs of C-H⋯O hydrogen bonds, forming chains along [101]. The solvate mol-ecules are linked to the chain by a C-H⋯O(tetra-hydro-furan) hydrogen bond. A combination of thermal analysis and powder X-ray diffraction revealed that title compound desolvated into epalerstat Form II. One C atom of the tetra-hydro-furan solvate mol-ecule is positionally disordered and has a refined occupancy ratio of 0.527 (18):0.473 (18).

Synthesis and Structure of Alkylzinc 3,5-Diphenylpyrazolates: Dramatic Influence of Steric and Solvent Effects.

The reaction of R2Zn (R = Et, (t)Bu) with 3,5-diphenylpyrazole results in the formation of three structurally diverse alkylzinc pyrazolates: a novel dinuclear tetrahydrofuran solvate, an unprecedented trimeric structure, and a spiro trinuclear aggregate. Structural analysis of the resulting complexes provides a new look at the aggregation and stabilization of alkylzinc species.

Thermal characterization of some polymorph solvates of the anti-inflammatory/anti-cancer sulindac

Solvates of sulindac were obtained by crystallization from acetone, chloroform, dichloromethane and tetrahydrofuran, but not from water, methanol, ethanol and propanols, acetonitrile and ethyl acetate and were studied by thermal (differential scanning calorimetry—DSC, thermogravimetry—TGA and thermomicroscopy—HSM) and spectroscopic (micro-Raman, SEM, X-EDS) analysis.It emerged from the thermal analysis that the samples thus obtained are not simple solvates or pseudo-polymorphs, but rather polymorph solvates, where the new form could be evidenced only after desolvation in controlled conditions, since the desolvation and polymorph transition processes occur together and in the thermogram the endotherms overlap. Desolvation, that is accompanied by decoloration of the sample from orange to yellow, enabled calculation of the solvate stoichiometry by the TGA parameters. The polymorph obtained from desolvation of the acetone solvate displays different thermal parameters from those obtained with chloroform, dichloromethane and tetrahydrofuran solvates. According to the solvents employed for crystallization, these thermal events leave sulindac in the form I or both I and II, outlining the very complex nature of the solid state of this drug. A new unsolvated polymorph form was directly obtained applying the technique of the quasi emulsion solvent diffusion (QESD). These results could open new perspectives in the use of the anti-inflammatory/anti-cancer sulindac in terms of formulation and mode of delivery and release.

Novel paste electrodes based on phosphonium salt room temperature ionic liquids for studying the redox properties of insoluble compounds

A new carbon paste electrode is described, which contains the room temperature ionic liquid (RTIL) tri(tert-butyl)(dodecyl)phosphonium tetrafluoroborate as binder. The advantages of this electrode are a high conductivity, very wide electrochemical window (5.6 V from 2.7 to −2.9 V, one of the widest ever reported for RTILs), stability in time, and reproducibility. This RTIL-carbon paste electrode (CPE) allows determining the current-voltage characteristics of redox-active compounds. Thus, the newly synthesized insoluble compound poly-tris(μ2-1,1′-ferrocenediyl-phenylhydrophosphinato-phenylphosphinato)-iron(III) tetrahydrofuran solvate {μ2-[FeII(η5-C5H4–P(PhOO)(η5-C5H4–P(PhOOH))]3FeIII}·THF was studied, and a quasi-reversible three-electron oxidation could be observed at a potential more positive than that of ferrocene. A comparison of voltammograms on the paraffin-CPE and on the novel RTIL-CPE shows the advantages of the latter.

Reversible Guest Removal and Selective Guest Exchange with a Covalent Dinuclear Wheel-and-Axle Metallorganic Host Constituted by Half-Sandwich Ru(II) Wheels Connected by a Linear Diphosphine Axle

The organometallic unit {[(p-cymene)RuCl2]2[4,4′-bis(diphenylphosphino)biphenylene]} has been revealed to be a good building block for the construction of wheel-and-axle (waa) crystalline scaffolds able to incorporate different organic solvents. In fact, the synthesis carried out in tetrahydrofuran (THF), dichloromethane, toluene, and p-xylene led to the corresponding solvates. An apohost could instead be isolated from diethyl ether. However, this showed a lower crystallinity than the solvates, as usually expected for waa compounds. Thermal extrusion of THF led to a new apohost framework. The desolvation process occurred with partial loss of crystallinity which, however, was completely restored after sorption of THF vapors with rebuilding of the starting THF solvate. THF could also be exchanged with p-xylene by a vapor uptake process, while exposure to other aromatics, such as benzene, toluene, and o- and m-xylene led to partial guest exchanges. The use of a more branched guest, such as p-cymene, complete...

Structural Correspondence of Solution, Liquid Crystal, and Crystalline Phases of the Chromonic Mesogen Sunset Yellow

The azo dye, sunset yellow, is a prototypical, chromonic liquid crystal in which assembly in aqueous solution at high volume fraction leads to lyotropic mesophases with a “package of properties distinct in almost every aspect” (Lydon, J. Curr. Opin. Colloid Interface Sci. 2004, 8, 480). In particular, the isotropic to nematic transition in such phases, the consequence of stacking of dye molecules in chains, is difficult to bring into correspondence with athermal theories for rigid rods as well as modifications that consider chain interactions with one another. Chromonic mesogens, small molecules that stack to form lyotropic liquid crystals, prompt structural questions that have yet to be answered; a full understanding of structure should inform colligative properties. Herein, the single crystal structure of a guanidinium salt of the sunset yellow dianion, a known chromonic mesogen, is reported. The compound crystallizes as a dihydrate, tetrahydrofuran solvate in the orthorhombic space group Pnna, with a =...

Synthesis and Structural Characterization of Molybdenum(VI) and Iron(II) Coordination Compounds with S-Alkyl-N-methyl-S-(2-pyridyl)sulfoximines and Catalytic Epoxidation Activity of the Molybdenum Complexes

Coordination compounds oxido(diperoxido)(S-butyl-N-methyl-S-(2-pyridyl)sulfoximine)molybdenum(VI), [MoO(O2)2{SO(NMe)(n)Bu(NC5H4)}] (5c), and bis{(dichlorido)(N,S-dimethyl-2-pyridylsulfoximine)iron(II)}, tetrahydrofuran solvate (1:1) (6), [FeCl2{SO(NMe)Me(NC5H4)}]2·THF are prepared from the free ligand 4 and molybdenum(VI) oxidediperoxide(dihydrate) and iron dichloride, respectively. The crystal structures reveal a trigonal bipyramid with the pyridine ring and the single oxygen on molybdenum in a trans arrangement for 5c and a planar μ(2)-Cl2Fe2 ring with trans-oriented exocyclic Cl atoms for 6 whereas the structures of the N,N-dicoordinated ligands are only little effected by the metals. Coordination compounds (5) efficiently catalyze the epoxidation of cyclooctene or of monosubstituted alkenes by tert-butyl hydroperoxide.

Characterization of Cyclopentyllithium and Cyclopentyllithium Tetrahydrofuran Complex

The solid-state structures of unsolvated, hexameric cyclopentyllithium and tetrameric cyclopentyllithium tetrahydrofuran solvate were determined by single-crystal X-ray diffraction. Cyclopentyllithium easily crystallized in hydrocarbon solvents. Solution-state structural analyses of cyclopentyllithium and cyclopentyllithium-tetrahydrofuran complexes in toluene-d8 were also carried out by diffusion-ordered NMR spectroscopy with diffusion coefficient-formula weight correlation analyses and other one- and two-dimensional NMR techniques. The solution-state studies suggest that unsolvated cyclopentyllithium exists as hexamer and tetramer equilibrating with each other. Upon solvation with tetrahydrofuran, cyclopentyllithium exists mostly as a tetrahydrofuran tetrasolvated tetramer.

Polymorphism through Desolvation of the Solvates of a van der Waals Host

2,4,6-Triethyl-1,3,5-tris(phenoxymethyl)benzene (1H), a van der Waals host molecule, forms 10 solvates with 1,4-dioxane (DXN), p-xylene (PXL), pyridine (PYD), chloroform (CLF), tetrachloromethane (TCM), tetrahydrofuran (THF), benzene (BEN), and ethyl acetate (EAC), which exhibit conversion to three different phases upon desolvation. Crystal structures of two of the guest-free phases were identified by producing single crystals of 1H from acetonitrile and ethyl acetate solutions. These two forms are converted to the third form upon heating. The third phase is also obtained after desolvation of the 1,4-dioxane solvate, but no single crystals corresponding to this phase could be isolated. Crystallization from THF and TCM produced two different solvates concomitantly in each case, whereas the EAC solution of 1H concomitantly produced the guest-free form II as well as minor quantities of a solvate. One of the THF solvates is isostructural to the CLF solvate, and the other THF solvate is isostructural to one of the TCM solvates.

Structural and electrochemical properties of β-tetrabromo-mesotetrakis(4-alkyloxyphenyl)porphyrins and their metal complexes

Crystal structure of 2,3,12,13-tetrabromo-5,10,15,20-tetrakis(4-butyloxy phenyl)porphinato copper(II) tetrahydrofuran solvate was examined and it features enhanced non-planar distortion of the porphyrin ring. The normal coordinate structural decomposition (NSD) analysis for the out-of-plane displacement of atoms of the macrocyclic ring in CuT(4-CnP)PBr4 (n = 4, 6) indicates mainly saddled distortion combined with small contribution from wave conformation. The electrochemical studies on MT (4-CnP)PBr4 (M = 2H, Cu(II), Zn(II)) revealed cathodic shift in redox potentials in contrast to the corresponding brominated porphyrins, MTPPBr4. This is perhaps due to non-planarity of the porphyrin ring and the positive inductive effect of the alkyloxy groups.

(Dibenzo-18-Crown-6)ammonium bromide tetrahydrofuran solvate: Synthesis and crystal structure

A new compound, (dibenzo-18-crown-6)ammonium bromide tetrahydrofuran solvate [NH4(Db18C6)]+ · Br− · THF (I), is synthesized and studied by X-ray diffraction analysis. The crystals of compound I are triclinic: a = 8.848 A, b = 9.696 A, c = 16.023 A, α = 73.75°, β = 86.93°, γ = 78.06°, Z = 2, space group P\( \bar 1 \). The structure of compound I is solved by a direct method and refined by full-matrix least squares in the anisotropic approximation to R = 0.095 by 5624 independent reflections (CAD-4 automated diffractometer, γMoKα). The Db18C6 molecule in structure I has a butterfly conformation with approximate symmetry C2v. The NH4+ cation where three disordered H atoms form hydrogen bonds with all six O atoms of the Db18C6 molecule is situated in the center of the cavity of the eighteen-membered macrocycle of the Db18C6 molecule. One ordered H atom of the NH4+ cation forms a strong hydrogen bond with the Br− anion.

Tetra-μ-acetato-bis{[1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]rhodium(II)}(Rh—Rh) tetrahydrofuran tetrasolvate

In this paper, we compare and discuss the very different crystal structures and supramolecular arrangements obtained when using different crystallization solvents with the same organometallic moiety. The new title tetrahydrofuran (THF) solvate, [Rh(2)(C(2)H(3)O(2))(4)(C(27)H(36)N(2))(2)] x 4 C(4)H(8)O, is compared with the toluene trisolvate reported previously by us [Góis, Trindade, Veiros, Andre, Duarte, Afonso, Caddick & Cloke (2007). Angew. Chem. Int. Ed. 46, 5750-5753]. The molecular structures of the two complex molecules display a similar conformation, but due to the presence of different solvent molecules, the two solvates crystallize in different space groups and exhibit quite diverse supramolecular assemblies. The toluene solvate crystallizes in the triclinic space group P1, while in the presence of THF, the monoclinic P2(1)/c space group is obtained, with the complex molecule residing on an inversion centre. The resulting crystal packing displays no classical hydrogen bonds but different supramolecular synthons give rise to different packing motifs. In this work, we highlight the different supramolecular architectures obtained when organometallic moieties crystallize with different solvent molecules. We compare the novel structure of the THF derivative with that of the toluene solvate of a dirhodium(II) complex belonging to a new family of catalyst compounds exhibiting very high performance in arylation processes.